The invention relates to an arrangement of nucleic acid sequences and their use.
With methods of the comparative genomic in situ hybridization (CGH) of reference chromosome preparations of normal Karyotype, it is now possible to determine in a genomic test DNA (for example, tumor DNA, with the suspicion for the existence of unbalanced chromosome aberrations) gains and losses of genoma sections of about 10 Mbp. With amplifications, it is also possible to chart substantially smaller DNA sections by CGH on reference chromosome preparations. These methods are known from Du Manoir, S.; Speicher, M. R.; Joos, S.; Schrock, E.; Popp, S.; Dohner, H.; Kovacs, G.; Robert-Nicoud, M.; Lichier, P.; Cremer, T.; "DETECTION OF COMPLETE AND PARTIAL CHROMOSOME GAINS AND LOSSES BY COMPARATIVE GENOMIC IN SITU HYBRIDIZATION". Hum. Genet. 90:590-610, 1993 or Joos, S.; Scherthan, H.; Speicher, M. R.; Schlegel, J.; Cremer, T.; Lichter, P.; "DETECTION OF AMPLIFIED GENOMIC SEQUENCES BY REVERSE CHROMOSOME PAINTING USING GENOMIC TUMOR DNA AS PROBE"., Hum. Genet. 90: 584-589, 1993. As genomic reference-DNA, DNA may be used which, if available, can be gathered from cells with a normal chromosome complement thereof or from another person.
With today's state of the art of (CGH, there are two essential limitations. First a further increase of the resolution capability is desirable. It is expected that, with prometa phase chromosomes, CGH analyses of partial trisomy and monosomy with a resolution capability of .gtoreq.3 Mbp become possible. This corresponds to an average DNA content of banded chromosomes with a high resolution chromosomal bands with about 1000 bands per haploid chromosome set. However, for many applications, a CGH test would be desirable by which gains and losses of particular genes or even intragenic DNA sections could be safely determined. It is possible that a better resolution can be achieved if the CGH analyses are performed with even more decondensed chromatin structures. On the other hand, CGH for mitotic reference chromosomes have the disadvantage that the fully automatic identification of chromosomes by fluorescence banding for example with DAPI and measurement of the CGH fluorescence quotient is complicated and time-consuming.
It is the object of the invention to provide an arrangement of nucleic acid sequences by which, with relatively little technical expenses automation and substantially improved resolution can be achieved.